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Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells.
Cell Death Differ. 2000 Jan; 7(1):102-11.CD

Abstract

The pro-apoptotic protein, Bax, has been reported to translocate from cytosol to mitochondria following exposure of cells to apoptotic stresses including cytokine withdrawal and treatment with glucocorticoids and cytotoxic drugs. These observations, coupled with reports showing that Bax causes the release of mitochondrial cytochrome c, implicate Bax as a central mediator of the apoptotic process. In this report we demonstrate by subcellular fractionation a significant shift in Bax localization from cytosol to cellular membranes in two human tumor cell lines exposed to staurosporine or etoposide. Immunofluorescence studies confirmed that Bax specifically relocalized to the mitochondria. This redistribution of Bax occurred in concert with, or just prior to, proteolytic processing of procaspase-3, activation of DEVD-specific cleavage activity and degradation of poly(ADP-ribose) polymerase. However, Bax membrane translocation was independent of caspase activity as determined using the broad-range caspase inhibitor z-VAD-fmk. High level overexpression of the anti-apoptotic protein Bcl-2 prevented Bax redistribution to the mitochondria, caspase activation and apoptosis following exposure to staurosporine or etoposide. These data confirm the role of Bax in mitochondrial cytochrome c release, and indicate that prevention of Bax translocation to the mitochondrial membrane represents a novel mechanism by which Bcl-2 inhibits drug-induced apoptosis.

Authors+Show Affiliations

Department of Microbiology, University of Louisville, Louisville, Kentucky, KY 40202, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10713725

Citation

Murphy, K M., et al. "Bcl-2 Inhibits Bax Translocation From Cytosol to Mitochondria During Drug-induced Apoptosis of Human Tumor Cells." Cell Death and Differentiation, vol. 7, no. 1, 2000, pp. 102-11.
Murphy KM, Ranganathan V, Farnsworth ML, et al. Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ. 2000;7(1):102-11.
Murphy, K. M., Ranganathan, V., Farnsworth, M. L., Kavallaris, M., & Lock, R. B. (2000). Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death and Differentiation, 7(1), 102-11.
Murphy KM, et al. Bcl-2 Inhibits Bax Translocation From Cytosol to Mitochondria During Drug-induced Apoptosis of Human Tumor Cells. Cell Death Differ. 2000;7(1):102-11. PubMed PMID: 10713725.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. AU - Murphy,K M, AU - Ranganathan,V, AU - Farnsworth,M L, AU - Kavallaris,M, AU - Lock,R B, PY - 2000/3/14/pubmed PY - 2000/6/17/medline PY - 2000/3/14/entrez SP - 102 EP - 11 JF - Cell death and differentiation JO - Cell Death Differ VL - 7 IS - 1 N2 - The pro-apoptotic protein, Bax, has been reported to translocate from cytosol to mitochondria following exposure of cells to apoptotic stresses including cytokine withdrawal and treatment with glucocorticoids and cytotoxic drugs. These observations, coupled with reports showing that Bax causes the release of mitochondrial cytochrome c, implicate Bax as a central mediator of the apoptotic process. In this report we demonstrate by subcellular fractionation a significant shift in Bax localization from cytosol to cellular membranes in two human tumor cell lines exposed to staurosporine or etoposide. Immunofluorescence studies confirmed that Bax specifically relocalized to the mitochondria. This redistribution of Bax occurred in concert with, or just prior to, proteolytic processing of procaspase-3, activation of DEVD-specific cleavage activity and degradation of poly(ADP-ribose) polymerase. However, Bax membrane translocation was independent of caspase activity as determined using the broad-range caspase inhibitor z-VAD-fmk. High level overexpression of the anti-apoptotic protein Bcl-2 prevented Bax redistribution to the mitochondria, caspase activation and apoptosis following exposure to staurosporine or etoposide. These data confirm the role of Bax in mitochondrial cytochrome c release, and indicate that prevention of Bax translocation to the mitochondrial membrane represents a novel mechanism by which Bcl-2 inhibits drug-induced apoptosis. SN - 1350-9047 UR - https://www.unboundmedicine.com/medline/citation/10713725/Bcl_2_inhibits_Bax_translocation_from_cytosol_to_mitochondria_during_drug_induced_apoptosis_of_human_tumor_cells_ L2 - https://doi.org/10.1038/sj.cdd.4400597 DB - PRIME DP - Unbound Medicine ER -